AND METHYLGRIGNARD REAGENTS WITH 2]%DIPHENYL-4-BUTANOLACTONES Oct. 5, 1953 ETHYL [JOINT CONTRIBUTION FROM THE W M . H. CHANDLER CHEMISTRY LABORATORY, LEHIGHUNIVERSITY, AND AND DEVELOPMENT DIVISION,SMITH, KLINEAND FRENCH LABORATORIES]
4731
THERESEARCH
The Reaction of Grignard Reagents with Lactones. I. Ethyl and Methyl Grignard Reagents with 2,2-Diphenyl-4-butanolactones BY NELSONR. EASTON, CARLA. LUKACH,'~ VELMERB. FISHAND PAUL N. CRAIG'~ RECEIVED MAY1, 1953 The abnormal reaction of 2,2-diphenyl-4-pentanolactone with ethylmagnesium bromide is shown to give a glycol, which results from both addition of and reduction by the Grignard reagent. This abnormal reaction is also found to occur with 2,2-diphenyl-4-butanolactone. However, methyl Grignard reagent was found t o react in a normal fashion with the pentanolactone to give 4,4-diphenyl-5-methyl-2,5-hexanediol. Reduction of 2,2-diphenyl-4-pentanolactonewith lithium aluminum hydride gives 2,2-diphenyl-l,4-pentanediol. The 1,4-glycolsare readily converted t o tetrahydrofuran derivatives with alcoholic hydrogen chloride, and were characterized as acetates.
The reaction between an aliphatic Grignard The dehydration product B did not react with reagent and a lactone such as butyrolactone pro- bromine, in contrast to cyclic vinyl ethers such as ceeds in a normal fashion to form a glycol, which 1114and cr-methylenecoumaran,Bwhich readily give results from the addition of two moles of Grignard bromine substitution products. Oxidation of comreagent2 The reaction may be formulated to pound B with potassium permanganate gave benzoproceed in a stepwise fashion by the initial forma- phenone] which showed that no phenyl rearrangetion of a cyclic hemiacetal (e.g. I1 below) which is ment had occurred. The analytical data showed tautomeric with a hydroxyketone. The second that compound A could not be the glycol (IV), step would then involve the action of another mole which would result from the normal addition of two of Grignard reagent to give the glycol. moles of Grignard reagent to the lactone. The reaction of ethylmagnesium bromide with Structures V and VI agree well with the an2,2-diphenyl-4-pentanolactone(I) was studied by alytical data for A and B, respectively, and are Wilson13 who formulated the product A as the compatible with the chemical evidence. cyclic hemiacetal (11). Wilson dehydrated the OH OH product A and assigned to the resulting compound C Z H S ) ~ (C&,)z-C-&H-CzHs B the structure of 3,3-diphenyl-5-methy1-2- (C&)z-C-L-( I I ethylidenetetrahydrofuran (111). CHz
0
(C6Hs)z-C-C
1
II
>o
CzH6MgBr -A-B
CHIOH
( C,yHs)z-C--C-C2Hs
I > .
CH3-CHOH I IV
CHs-kHOH
v
H
HCl
CHz-CH CH3 I OH
CHz
I
I io CH-CH I
(C&,)pC-C=CH-cHa
' 2
I
CHz
I
CH3-CHOH
CHs
VI
VI1
Reduction of 2,2-diphenyl-4-pentanolactone with I I lithium aluminum hydride gives glycol (VII) bH3 CHI which is characterized by dehydration to 3,3111 I1 diphenyl-5-methyltetrahydrofuran and by formaTwo independent syntheses4 of compound I11 tion of a diacetate. Spectral data show the by different procedures gave a compound which similarities between compounds V and VII. The sequence of reactions used by Wilson was differed from Wilson's compound B. Therefore] and the the sequence of reactions reported by Wilson was applied to 2,2-diphenyl-4-b~tanolactone~ repeated and the resulting compounds were care- abnormal reaction again occurred to give 3,3diphenyl-l,4-hexanediol, which was transformed fully studied. Compound A was found to contain two active to the diacetate and to 3,3-diphenyl-2-ethyltetrahydrogen atoms by the Zerewitinoff determination.6 hydrofuran. The reaction of the methyl Grignard reagent with Moreover, it was found possible to form a diacetate from A with acetic anhydride and pyridine. (The 2,2-diphenyl-4-pentanolactonewould not be exmonoacetate obtained by Wilson was not obtained.) pected to give the abnormal product as the methyl Grignard reagent is not capable of facile reductions.8 (1) (a) Abstracted in p a r t from the thesis submitted in partial fulThis reaction proceeds in a normal fashion with the fillment of t h e requirements for the degree of Master of Science: (b) Smith, Kline and French Laboratories. formation of 4,4-dimethy1-5-methy1-2,5-hexanedio1, (2) S. Losanitch, Compt. vend., 163, 390 (1911); also B. I. Arventi, which was characterized by formation of the Chem. Zeiztu., 114, 11, 718 (1943); C . A . 38, 2338,5217 (1944). CH3-CH
CHz-
(3) W. Wilson, J . Chem. Soc., 1993 (1948). (4) N. R. Easton, S. J. Nelson, V. B. Fish and P. N. Craig, paper presented before t h e Organic Division, A.C.S. 122nd Meeting, Atlantic City, N. J., Sept. 18, 19.52; THIS JOURNAL 76, 3751 (1953). ( 5 ) P.M.Maginnity and J. B. Cloke, Anal. Chem., SO, 978 (1948).
(6) R. Adams and R. E. Rindfusz, THIS JOURNAL, 41, 648 (1919). (7) J. Attenborrow, J. Elks, B. A. Hems and R. N. Speyer, J . Chem. Soc., 510 (1949). (8) H.Gilman, "Organic Chemistry," 2nd Ed., Vol. I. John Wiley and Sons, Inc., New York, N. Y.,1943,p. 647.
4732
N. R. EASTON, C. A. LUKACH, V. B. FISHAND P. N. CRAIG
monoacetate and by dehydration to 3,3-diphenyl2,2,5-trimethyltetrahydrofuran. The isolation and structural determination of intermediates is now being attempted. Acknowledgment.-The authors wish to thank Drs. W. B. Whalley and S. J. Nelson for their helpful interest in this work. Spectral data were obtained by Mr. E. S. Rump, Jr., and Mr. P. A. Geary. Experimental 4,4-Diphenyl-2,5-heptanediol (V) .-The procedure used was identical with that employed by Wilson.a After three recrystallizations from methylcyclohexane, the product melted a t 123-124'. Active hydrogen was determined by the Zerewitinoff method.s A d . Calcd. for C1gHZ1O2: C, 80.24; H, 8.51; active hydrogen, 0.704. Calcd. for C19Hzz02 (11): C, 80.82; H, 7.86; active hydrogen, 0.356. Calcd. for CzlHzaOz (IV): C, 80.72; H , 9.03; active hydrogen, 0.64. Found: C, 80.00; H, 8.51; active hydrogen, 0.83. Found (Wilson*): C, 80.15; H , 8.3. 3,3-Diphenyl-2-ethyl-5-methyltetrahydrofuran(VI) .-
The procedure again was identical with that employed by Wilson.3 After recrystallization from methanol, the product melted a t 89.5-90.5". Anal. Calcd. for Cl9HZ20: C, 85.67; H , 8.33. Calcdfor C ~ ~ H ~ O O ( IC, I I86.32; ): H , 7.63. Found: C, 85.39; H , 8.28. Found (Wilson*): C, 86.0; H , 8.0. 4,4-Diphenyl-2 ,5-diacetoqheptaue.-The glycol ( V ) was refluxed with a mixture of acetic anhydride and pyridine for two hours. The solution was poured into water and the resulting mixture was extracted with ether. The ether layer was dried over magnesium sulfate and concentrated. The residue was taken up in petroleum ether and the oil which separated upon cooling gradually solidified. After recrystallization once from methanol and water, and twice from Detroleum ether, the Droduct melted a t 76-77'. Anat. Calcd. for CzsH?804: C, 74.98; H, 7.66. Found: C, 75.15; H , 7.60. 2,2-Diphenyl-l,4-pentanediol(VII).-A solution of 25 g. of lithium aluminum hydride in 250 ml. of anhydrous ether was prepared. Ten milliliters of this solution was added dropwise with stirring and cooling to a solution of 10.0 g. (0.04 mole) of 2,2-diphenyl-4-pentanolactonein 100 ml. of dry benzene. After five minutes, the mixture was decomposed with water. The resulting slurry was poured with stirring into a mixture of 200 ml. of ice and 25 ml. of concentrated sulfuric acid. The organic layer was washed twice with water and evaporated on the steam-bath to leave a solid, m.p. 111-113". Recrystallization from ethanol and water gave 8.4 g. (83%) of crystals, m.p. 114.0-115.5'. A mixed m.p. with the starting lactone was depressed below 100'. Anal. Calcd. for C I T H ~ ~ OC, ? : 79.65; H, 7.86. Found: C, 79.50; H, 8.03. 2,2-Diphenyl-l,4-diacetoxypentane.-Five grams of 2,2diphenyl-1,4-pentanediol(VII) was dissolved in 20 ml. of acetic anhydride. On the addition of 3 drops of sulfuric acid the mixture spontaneously warmed to 80". After 15 minutes on t h e steam-bath, the greenish mixture was poured into 300 ml. of water and stirred. After cooling the mixture, the oil solidified. A recrystallization from acetone-water (Darco) gave 4.5 g., m.p. 78-79.5' (68%). Anal. Calcd. for C21H240,: C, 74.09; H , 7.11. Found: C, 74.38; H , 7.33. Hydrolysis of this diacetate with aqueous alcoholic potassium hydroxide yielded only starting glycol, indicating that the sulfuric acid used did not cause a neopentyl-type rearrangement. 3,3-Diphenyl-5-methyltetrahydrofuran.-Prepared by the method used for compound VI (above), m.p. 46.3-18O (acetonewater). .4naZ. Calcd. for C17H180: C, 85.67; H , 7.61. Found: C, 85.69; H, 7.83. 3,3-Diphenyl-1 ,I-hexanediol.-Prepared by Wilson'sS enmil method using ethylmagnesium bromide and 2,2-
VOl. 7 5
diphenyl-4-butanolactone6;recrystallized twice from methvlcyclohexane, m.p. 130-131'. Anal. Calcd. for C18H2202: C, 79.96; H, 8.20; two active hydrogen atoms, 0.75. Found: C , 80.00; I T , 8.01; active hydrogen, 0.80. 3,3-Diphenyl-l,4-diacetoxyhexane.--Prcpared by the method given above for the acetylation of 4,4-diphenyl-2,5heptanediol, m.p. 95-96' (from ethanol). Sublimation a t 1 mm. did not alter the melting point. Anat. Calcd. for C221€?604:C, 7-4.57; H, 7.37. Found: C, 74.55; H , 7.58. 3,3-Diphenyl-2-ethyltetrahydrofuran.-Prepared by the method given above for the preparation of 3,3-diphenyl-2ethyl-5-methyltetrahydrofuran, m.p. 70-71' (from methanol). Anal. Calcd. for C18H200: C, 85.67; H , 7.99. Found: C,85.75,85.60; H,8.09,7.9;1. 4,4-Diphenyl-5-rnethyl-Z ,5-hexanediol.-Me thylmagnesium iodide was prepared from 9.72 g. (0.4 mole) of magnesium and 56.8 g. (0.4 mole) of methyl iodide, using a total of 125 ml. of ether. This Grignard solution was refluxed for 18 hours with a solution of 25.2 g. (0.1 mole) of 2,Z-diphenyl-4-pentanolactone in 100 ml. of benzene. The reaction was worked up in the usual manner. Recrystallization of the product from methanol gave white crystals, m.p. 184.5-185.5', 10 g. (36%). Anal. Calcd. for C1gH2402: C, 80.24; H , 8.51; two active hydrogen atoms, 0.70. Found: C, 80.21; H , 8.44; active hydrogen, 0.68. 4,4-Diphenyl-5-methyl-2,5-hexanediol Monoacetate.-This compound was prepared by the pyridine-acetic anhydride method described above. The acetylation is presumed t o occur on the secondary alcoholic group, as the tertiarv alcoholic group is sterically more hindered; m.p. 145.5-147' (from methanol and then sublimed). .4nal. Calcd. for C21H?603: C, 77.26; H, 8.03. Found: C, 77.15; H , 7.92. 2,2,5-Trimethyl-3,3-diphenyltetrahydrofuran.-The dehydration was carried out as reported for the preparation of 3,3-diphenyl-2-ethyl-5-methyltetrahydrofuran(VI). The product was recrystallized from methanol, m.p. 6566.5". Anal. Calcd. for CIgHi20: C, 85.67; H, 8.33. Found: C, 85.57; H , 8.33. 2,2-Diphenyl4-butanolactone.-This compound was prepared by the method of Attenborrow, et el., but the imidolactone was isolated by the method reporteds for the imidolactone in the preparation of 2,2-diphenyl-4-pentan~lactone~ The 3,3-diphenyl-2-furanoniminemelted a t 80.5-81.5 (from methylcyclohexane), and a mixture of this compound with 2,2-diphenyl-l-butanol:ictonc gave a large depression of the melting point. '4nal. C:ilcd. for ClJTljOX: S,5.90. Found: X, 5.70.
SPECTRAL DATA Ultraviolet
Com-
pound
A, mp
Infrared
E"
A> P
Assignment
254 403 3.10 sh. Bonded OH groups 260 475 3 . 2 1 264 sh. 420 270 sh. 290 VI 255 403 S o band a t (OH region) 3.00-3.25 m 260 480 KOband a t (C=O region) 5.00-6.00 m 264 460 271 355 VI1 254 Bonded OH groups 380 3.15 455 3.05 259 265 sh. 375 269 295 a Molar extinction coefficient in 95yo ethanol. BETHLEHEM A N D P H I L A D E L P H I A , PEXX.4 V
1
(9) N. R. Easton, J. H. G a r r l n ~ rand J. R. Stevens, THISJ O U R N ~ P ~ 69, 2941 (1947).
